6.3. Is HIV the cause of AIDS? What is AIDS?
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This article is from the AIDS FAQ, by Dan Greening with numerous contributions by others.
6.3. Is HIV the cause of AIDS? What is AIDS?
by Robert Holzman and David Mertz
The immune system is responsible for defending the body against
bacteria, parasites, viruses and cells identified as foreign such as
virally infected, transplanted, and (many believe) malignant
cells. The Acquired Immune Deficiency Syndrome (AIDS) is a condition
in which a person's immune system is so weakened that s/he becomes
susceptible to conditions that occur rarely in those with intact
function. The formal case definition includes a large number of
indicator diseases deemed, in the words of the original: "at least
moderately predictive of cellular immune deficiency". This original
definition, free of assumptions regarding etiology, has been modified
in accordance with the general acceptance of HIV as the causal agent
responsible for the vast majority of AIDS cases. The revised
definition also includes certain conditions believed ascribable to
advanced HIV infection itself (e.g. wasting). A concise summary of the
1993 case definition may be found in the textbook, Scientific American
Medicine section 7, chapter XI, page 2.
Q: Why is HIV considered to be the cause of AIDS?
The epidemic occurrence, in 1980, of Kaposi's Sarcoma in homosexual
men and, in 1981, of certain unusual infections in intravenous drug
users, were unprecedented events. While all of the initially
recognized diseases were previously known, and most were occasionally
seen in persons who were ostensibly immunologically normal, the risk
of developing them was strongly associated with the presence of an
immunosuppressed state, generally due to therapy for cancer or
suppression of graft rejection. In order to identify cases for study
and comparison with noncases, an operational definition was developed
(see the FAQ question What is AIDS?) The issue for investigators was
why so many homosexual men and intravenous drug users were developing
such severe immune suppression now, while previously only subtle
defects in immunity had been seen in such individuals.
Among the earliest suggestions of an infectious etiology was the
report (published in Am. J. Med. 1984;76:487-492, but presented orally
earlier) that cases of AIDS among homosexuals were not occurring
randomly but were clustered among sexual contacts. 40 persons were
identified who showed linked transmission over 3 generations of
infection. At the time there were four major theories of etiology
under investigation: (1) multiple and repeated infections with
Cytomegalovirus leading to immune suppression, (2) immunologic
exhaustion from multiple previous infections, (3) alloimmunization to
lymphocytes, due to intra-rectal injection of sperm, and (4) toxic
effects of components of inhalant drugs or genital
lubricants. Theories 2-4 were incompatible with the observed pattern
of transmission. No credible evidence for theory 1 was ever produced.
Three laboratories, Gallo's at NIH, Levy's at UCSF, and Montagnier's
at Institute Pasteur (listed alphabetically), almost simultaneously
identified a retrovirus in AIDS patients which was ultimately named
the Human Immunodeficiency Virus (HIV). The identification of
infection with this retrovirus in most (and with subsequent
improvements in technique, in almost all) persons with AIDS who were
tested raised the question whether this virus was a harmless infector,
an opportunistic pathogen, or the actual causal agent of the
progressive immunosuppression. Some of the evidence for the last role
is summarized below.
First, HIV causes a distinct acute illness (the "primary infection")
which has been characterized in otherwise healthy
(non-immunosuppressed) individuals known to have been or suspected of
having been infected at a particular time (e.g. in a laboratory
accident) or in whom the appearance of serum antibodies was detected,
indicating a recent infection. An causal role for HIV in subsequent
immune suppression is suggested by the fact that those whose symptoms
of primary infection last more than 14 days subsequently develop AIDS
more rapidly than persons who have briefer periods of
illness. (Br. Med J. 1989;299:154-157.)
Second, HIV infects cells with the CD4 receptor on their surface,
cells which are critical for immune function and which, in those with
AIDS, are abnormal in function, number, or both. (For a discussion of
current concepts of the pathogenesis of HIV-related immune suppression
see Science 1993; 262:1011-1018.)
Third, HIV infection antedates immune suppression and is the single
factor common to all AIDS risk groups. Studies of stored blood
indicate that HIV spread in the homosexual population of San Francisco
a few years before the epidemic of AIDS-indicative
conditions. Moreover, in cases where the date of infection is known
exactly or approximately, acquisition of HIV infection precedes the
development of immune suppression by substantial periods. Such
situations include, for example, transmission by transfusion to adults
having cardiac surgery or neonates with hemolytic disease, by breast
milk to neonates (including breast milk of a wet nurse to a child
without familial risk factors), by clotting factor concentrates to
hemophiliacs, by parenteral exposure of laboratory technicians or
physicians to blood or viral concentrates, and to spouses of HIV
infected persons via sexual transmission. Most telling is the
observation that among infants of HIV-infected mothers, only those
that acquire HIV infection develop progressive immune suppression and
AIDS defining illnesses.
Not all accept the causal association between HIV and the immune
suppression that leads to an AIDS indicative illness. Peter Duesberg,
a retrovirologist at the University of California at Berkeley has been
the most vocal scientific critic of this hypothesis. Few of those
actively engaged in research on AIDS agree with Duesberg's analysis,
and rebuttals may be found in Nature 1990; 345:659-660 and Science
1988; 241:514-517. At least one study (M.S.Ascher, Nature, 1993;
362:103) has been designed in response to his assertions that drug use
was a major cause of AIDS associated immune suppression. In that
study, cohorts of homosexual and heterosexual men were compared,
matched for use of marijuana, cocaine or amphetamines. There was no
association between the development of AIDS and use of these
drugs. The homosexual cohort used more nitrites than did the
heterosexual one, but development of AIDS was related to the presence
of HIV infection and not to use of drugs (M.S. Ascher, Lancet, 1993;
341:1223).
Those who believe that HIV causes AIDS look to the cases associated
with transfusion, congenital infection, or sexual transmission as
coming as close to Koch's postulates as is likely to be possible in
humans. In the absence of an animal model in which HIV induces immune
suppression, it is likely to be impossible to strictly fulfill Koch's
Postulates for HIV and AIDS.
As the reader studies the debate on the cause of AIDS and forms
his/her own conclusions it is important to focus clearly on the
arbitrary nature of the case definition as an operational way to
detect severe immune deficiency. Even the 1993 revision of the AIDS
case definition does not require the documented presence of HIV
infection. It is logically possible for there to be more than one
etiology, although published data (New Engl. J. Med, 1993;
328:373-379.) indicate that only 299 of 230,179 reported persons with
AIDS have been HIV-negative when testing was done (Evidence of HIV
infection was sought in approximately half the 230,179 (Duesberg,
Science, 1992;257:1848)).
In summary, to assert that HIV is the cause of AIDS is to assert that
HIV was the cause of the epidemic of immune suppression that appeared
in 1980-81. To ascribe this role to HIV it is not necessary to show
that HIV is the only cause of immunosuppression in those at risk, nor
that cofactors are unimportant in the development of AIDS, nor that
every patient who meets the case definition has HIV infection. It is
only necessary to show that HIV infection can result in immune
suppression and that HIV infection occurred in the appropriate
population at an appropriate time to account for the epidemic.
Q: What is the evidence against HIV as the cause of AIDS? (see also
Section 7.4: The Group for the Scientific Reappraisal of the HIV/AIDS
Hypothesis)
There are many PWA's and AIDS-activists, and many in the scientific
community who remain doubtful that HIV causes AIDS. These doubts arise
both from observers of the socio-political history of HIV/AIDS, and
from some scientists knowledgeable about retroviruses, epidemiology
and immunology.
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